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T Cell Activation and Clonal Selection

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...

GTPases and their Regulation

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...

GTPases and their Regulation

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...

T Cell Types and Functions

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...

The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Related Experiment Video

Updated: Jun 18, 2026

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Published on: April 16, 2012

The Tregs' world according to GARP.

Manuela Battaglia¹, Maria Grazia Roncarolo

¹San Raffaele Telethon Institute for Gene Therapy, Milano, Italy.

European Journal of Immunology

|November 12, 2009

Summary

GARP is a novel marker for activated regulatory T cells (nTreg), distinguishing them from effector T cells. This receptor binds to TGF-beta latency-associated peptide, offering new insights into nTreg-mediated immune suppression.

Area of Science:

Immunology
Cell Biology

Background:

Naturally occurring regulatory T cells (nTreg) are crucial for immune tolerance.
FOXP3 is an unreliable marker for human nTreg as activated effector T cells also express it.
The mechanisms of nTreg-mediated suppression are not fully understood.

Discussion:

GARP (Gated Receptor) is selectively expressed on activated human nTreg and nTreg clones, unlike activated effector T cells.
GARP directly binds to the latency-associated peptide (LAP) of TGF-beta.
GARP's role in nTreg-mediated suppression is clarified, though overexpression doesn't activate TGF-beta.

Key Insights:

GARP serves as a reliable marker for bona fide human nTreg.
GARP facilitates the binding of LAP to nTreg.

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Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

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Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol

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Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

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The interaction of GARP and LAP is central to understanding nTreg function.

Outlook:

Further research into GARP's precise role in TGF-beta regulation is warranted.
Targeting GARP could offer new therapeutic strategies for immune-related disorders.
This discovery advances the understanding of immune regulation and tolerance.